Flexible containers from polymer films are widespread for storing pharmaceutical substances solutions for dialysis, solutions for infusion and/or agents for nutrition. For opening filled containers or compartments of said containers, several materials and methods for producing peelable seals (peelable heatsealed welds) have been developed. In contrast to permanent welded seals, peelable seals can be ruptured by tensile force or by pressing on an adjacent container chamber that is filled with a liquid. It should be guaranteed to open the seal without damages to the container material or leakage. The peelable seal strength should be high enough for production and transport and still low enough to easily open the bag.
In order to simplify the opening of peelable seals, such seals have been provided with so-called rupture zones, whereby the opening force is locally reduced and the manual opening of the peelable seals is facilitated. Such seal can readily be opened by different handling techniques.
European patent document EP 0 700 280 concerns a multi-layer polymer film for a multi-chamber medical bag for preparation of mixed medical solutions, which has at least two chambers which are separated from each other by a peelable seal. European patent document EP 0 700 280 suggests a V-shaped rupture zone. In this case, the seal opens first at the point of the V since the highest force on the seal is created there.
European patent document EP 0 893 982/International Publication Number WO97037628 relates to flexible polymeric containers with an improved long term storage capacity for parenterally administered medical fluids. The container comprises an outer sealed airtight envelope and an inner container filled with one or several medical agents. The inner container comprises peelable seals having rupture zones. The rupture zones of the peelable seals are V-shaped and, therefore, comprise a point where two straight seams meet in an angle. A small or sharp angle will be easy to rupture by the user, but it will at the same time create a risk for unintentional opening when handling the container. In contrast, a very large angle will provide a seam that is difficult to open. Therefore, European patent document EP 0 893 982 suggests an angle of the seals in the rupture zone of 120° to 140°.
A first preferred opening procedure mentioned in European patent document EP 0 893 982 is to gently roll up the container from the upper side and thereby make use of the volume of the largest chamber to exert a pressure large enough to rupture the seal in its weakest point and peel apart the seam towards the sides of the container. This technique is designated as the rolling method. Another preferred way of opening the seal is to pull the front and the rear walls of the inner container apart from one another by a careful pulling motion so a rupture is formed in the weakest spot of the seal which thereby may be easy to peel apart. This technique is designated as the pulling method.
The document further describes a rupture zone having two straight seams meeting in a region formed as a curved part. The rupture zone still comprises straight sections.
The two most common complaints concerning medical containers with a peelable seal are: (1) peelable seals are already opened at arrival to customer and (2) a film failure when opening peelable seals.
There is always a balance between the demands to have a peelable seal that is strong enough to withstand the manufacturing process and is easy to open for the customer. Flexible containers with peelable seals of low seal strength, e.g. 5 to 10 N/30 mm, can be readily opened, but seals of low strength can be damaged during manufacturing and transport.
For this reason, it is advantageous to manufacture peelable seals with a seal strength at least 30 N/30 mm, and preferably 40 N/30 mm. However, the inventors have found that the polymeric film is frequently torn when the peelable seal with a V-shape as disclosed in European patent document EP 0 893 982 and a strength of at least 30 N/30 mm is opened by the pulling method, resulting in leakages in the bag. This problem might be avoided by using the rolling method, which should allow a more controlled opening by applying a more even pressure on the weak seal.
The inventors have, however, found that the V-shaped rupture zone according to EP 0 893 982 shows a relatively high resistance against manual opening of the seals by the rolling method when the seal strength is equal or higher than 30 N/30 mm.
High resistance against opening means that a higher burst pressure registered inside the liquid-filled bag is required for opening the seal. It is a major drawback for the user in daily routine when a relatively high burst pressure is required for opening peelable seals. Thereby, the handling of the bag is impaired. By applying a high burst pressure, the seal opens rapidly in one step instead of opening at first in the rupture zone and peeling slowly apart towards the sides of the container in a second step.
When a container with three chambers is used which are filled with different solutions, a sudden and fast opening of peelable seals is undesirable, because it is not possible to control which seal is opened at first. Even though the bag-design is the most important point for a controlled mixing order of the chambers contents, an uncontrolled opening of the seals as mentioned above might also result in a uncontrolled mixing of the bag contents.
In order to reach a controlled opening of the peelable seals, it is desired that the rupture zone opens in a first step and in a second step the remaining part of the peelable seal opens. Experiments of the inventors have shown that this can hardly be reached with conventional V-shaped seals, especially when V-shaped seals are hard to open due to high seal strengths of at least 40 N/30 mm.
An object of the present invention is to provide a container with a peelable seal that can be readily opened without the danger of destroying the container. In particularly, it is an object of the present invention is to provide a flexible container with a well functioning peelable seal design, wherein the seal should be easy to open when the seal strength is ≦40 N/30 mm; the seal should not open by slight pressure on the bag that occurs during storage and transport; the seal should not open rapidly and in one step, the seal may open in two steps—first the rupture zone and then the remaining part; and the seal should open by rolling as long as the seal is peelable—in this case, the seal should easily open up to seal strengths of 40 N/30 mm.
The above mentioned objects may be attained by a container made of a flexible polymeric film comprising at least one peelable seal having at least two substantially straight sections which are connected by a rupture zone, wherein the rupture zone of the peelable seal is curved over its whole length between the straight sections.
The one or more rupture zones of the peelable seal connect substantially straight sections of the peelable seal. Substantially straight means that said sections can either be absolutely straight or minimally bent with respect to the dimensions of the container. Preferably, the sections that are connected by the curved rupture zone are absolutely straight.
A peelable seal according to the present invention can contain more than one rupture zone and more than two straight sections. However, it is preferred that it contains two straight sections that are connected by one rupture zone. In the latter case, the rupture zone is, in a specific preferred embodiment located in the middle of the peelable seal, resulting in two straight sections of equal length.
The rupture zone of the peelable seal is curved over its whole length between the straight sections. The term curved means that there are neither straight sections nor any kinks or angles within the rupture zone. A curved shape according to the present invention comprises circular shapes, S-shapes and ellipsoidal shapes and irregular curved shapes, wherein circular and ellipsoidal shape mean that the curved rupture zone is formed as an arc of a circle or an arc of an ellipse. It is to be understood in this connection that the terms “arc of an circle” or “arc of an ellipse” are equivalent to a segment of a circle or segment of an ellipse.
In an embodiment of the invention, the curved rupture zone of the seal is formed as an arc of a circle with a radius of 5 to 75 mm, more preferably 10 to 30 mm and most preferably 20 to 25 mm, wherein the radius is measured from the center of the circle to a point on the outer edge of the seal, wherein the outer edge is the edge that is more dislodged from the central point of the circle than the inner edge.
When the curved rupture zone is formed as an arc of a circle, said arc has preferably a central angle of at least 60°, more preferably 60° to 180°, especially 90° to 150°.
It is also advantageous that the rupture zone is S-shaped, wherein a preferred S-shape is made up of two connected half circles with a radius of 5 to 75 mm, more preferably 10 to 30 mm and most preferably 20 to 25 mm. The radius is again measured from the center of the circle to an outer edge of the seal.
The straight sections of the peelable seal can enclose an angle or the sections can be parallel to each other or in line with each other. When the straight sections form an angle, such angle is preferably from 120° to 180° and more preferably from 150° to 180°.
When the straight sections are parallel to each other, the distance (dislocation) between the straight parallel sections is preferably from 10 to 60 mm, more preferably 15 to 40 mm and most preferably 20 to 35 mm.
In an embodiment of the invention, the curved rupture zone is formed as an arc of a circle with a central angle of 90° and the straight sections are parallel to each other.
The width of the seal can vary between the straight sections and the rupture zone. In absolute values the seal width of the straight sections is preferably from 2 to 10 mm, more preferably from 5 to 8 mm, and the seal width of the rupture zone is from 2 to 10 mm, preferably from 5 to 8 mm. The width of the straight sections may be different than the width of the rupture zone. Preferably, however, the seal width of the straight sections and the seal width of the rupture zone are the same.
The rupture zone is preferably positioned in the middle of the seal, so it can be successively opened from the middle towards the sides, since this may enable a highly reproducible opening procedure by the user from the outside of the bag. The rupture zone typically has a length of less than half the entire seal, preferably less or equal than about 40% of the seal and more preferably less than about 30% of the seal length. In a more preferred embodiment of the present invention, the length of the rupture zone amounts to 3 to 10%, more preferably 5 to 7% of the length of the peelable seal. But it can also be advantageous when length of the rupture zone is 7 to 13%. In absolute values, the length of the rupture zone is preferably 20 to 40 mm.
In an embodiment of the invention, the container is made of a flexible polymeric film having a region with a higher melt point designated as its outside and having a region with lower melt point designated as its sealing inside which can be sealed together by means of conventional welding tools to permanent or peelable seals. It is to be understood that the inner region is intended to face the stored agent or agents and can form both permanent seals and different peelable seals when subjected to different welding conditions or operations.
The film may be made of at least two different polymer layers wherein the inside layer is a sealant layer that is capable of forming both permanent seals and peelable seals when subjected to welding at different temperatures.
A preferred multilayer polymer material for the manufacture of a container according to the present invention is described in European patent document EP 0 739 713 and known under the trademark Biofine™.
Another multilayer polymer material can have the following structure:
The inner sealant layer is preferably based on polyolefins, such as polyethylenes or polypropylenes of various qualities which are chemically inert to the stored fluids, autoclavable, weldable and possible to recycle. The terms “polyethylenes” and “polypropylenes” are intended to include both homopolymers and copolymers having such mentioned characteristics unless otherwise is specified. Preferably, the sealant layer is based on a polyethylene homopolymer, a polyethylene copolymer, a polypropylene homopolymer, a polypropylene copolymer a polyethylene-polypropylene-copolymer and/or a mixture of polypropylene with polyethylene.
It is preferred for the inner, sealant layer to comprise a high amount of polyolefin, especially polypropylene, in order to benefit from its capacity of being inert towards the stored fluids and for facilitating the manufacturing of a container by means of different welding techniques. It is especially preferred that this layer can form both leaktight, but controllably rupturable, peelable seals at a predetermined temperature and permanent highly consistent seals when welding it together with different conditions such as different welding temperatures or welding pressures.
However, since many conventional polyolefins, in particular polypropylenes, often have an insufficient flexibility and a certain brittleness, it is desirable to combine them with a polymer having an elastic property. In an embodiment according to the present invention, it is therefore preferred to combine the polyolefin of the sealant layer with a supplementary elastomer to improve its flexibility and resilience.
The thermoplastic elastomer that may be compounded with the polyolefin in the inner sealant layer is preferably selected from the group comprising a styrene-ethylene/butylene-styrene-triblock polymer (SEBS), a styrene-ethylene/propylene-styrene-triblock polymer (SEPS), a styrene-butadiene-styrene-triblockpolymer (SBS), and/or a styrene-isoprene-styrene triblock polymer (SIS).
The outer layer preferably comprises a flexible polymeric material with a high melting point that provides the material with an improved stability at the high temperatures locally reached during the welding. Suitable materials can be found among certain polyesters and copolymers thereof (copolyesters) and in particular cycloaliphatic polyesters.
There may be at least one interior layer between the outer layer and the inner sealant layer comprising an thermoplastic elastomer.
Another material that is suitable for the type of containers according to the present invention is Excel™ from McGaw Inc., a multilayered polymeric material of about 200 micrometer thickness which is described in the European patent document EP 0 228 819. Excel™ has a multilayered structure substantially comprising: a) an inner, sealant layer facing the medical fluid consisting of a mixture of a polyethylene/polypropylene copolymer (FINA Dypro Z 9450) and KratonB G1652 from Shell (a styrene/ethylene/butadiene/styrene (SEBS) copolymer); b) a middle, tie layer of pure KratonB G1652; and c) an outer, release layer of Ecdel™ B 9965 (or 9566 or 9967) from Eastman Chemical Co, which is a cycloaliphatic thermoplastic copolyester (a copoly(ester ether), a condensation product of the trans isomer of 1,4-dimethyl-cyclohexanedicarboxylate, of cyclohexanedimethanol and hydroxyterminated polytetramethylene glycol).
Other types of multilayered polymeric films, such as those described above may also be used in the present invention. Such other types of multilayered polymeric films may be made of at least two different polymer layers, wherein the inside layer is a sealant layer that is capable of forming both permanent seals and peelable seals are described in European patent document EP 0 893 982, European patent document EP 0 700 280 and International Publication Number WO 01/42009, as well as methods for their production and methods for welding peelable seals.
The container or bag with peelable seals as described before may be enclosed in an overpouch with a high oxygen barrier. The overpouch film may be a multi-layer structure including PET, a thin glass coating and polypropylene. Suitable overpouches are for example described in European patent document EP 0 893 982. An oxygen absorber may be placed between the container and the overpouch.
An embodiment of the present invention provides a method for forming the inventive container and a method for forming the above described peelable seal. Generally, hot bar heat sealing or impulse heat sealing processes may be used for producing permanent and peelable seals according to the present invention.
Suitable peelable seal welding temperatures for the above mentioned Biofine™ films are in the range of 122 to 130° C. Such seals are suitably leaktight after being subjected to conventional mechanical package tests and are objectively easy to open. They are also suitably leaktight after the container has been subjected to steam sterilization. Suitable welding temperatures for forming permanent seals with Biofine™ film are in the range of 130 to 160° C.
When Excel™ is used as multilayer film material for the manufacture of containers, the temperature for welding peelable seals is 113 to 120° C. and the temperature for welding permanent seals is 130 to 160° C.
In an embodiment of the present invention, the container, as described above, may be used for storing pharmaceutical substances, solutions for dialysis, solutions for infusion and/or agents for nutrition.